Modern pharmaceutical discovery increasingly relies on combinatorial approaches to simultaneously generate millions of compounds with potential biological activity and on high-throughput screening to rapidly assay each of these compounds for selected biological activities. A basic rationale supporting these combinatorial synthetic methodologies is that producing larger, more diverse compound libraries increases the probability of finding novel compounds with significant therapeutic and commercial value. The field of combinatorial chemistry represents a convergence of chemical and biological disciplines, facilitated by fundamental innovations in miniaturization, robotics, and receptor development.
Combinatorial chemistry includes systematic and repetitive organic synthetic techniques that utilize sets of chemical precursors or building blocks to form a diverse set or library of molecular species. Active compounds are typically identified within populations, either spatially, through chemical encoding, or by systematic, successive synthesis and biological evaluation or deconvolution. For example, in one common combinatorial organic synthetic approach two-dimensionally arrayed chemical precursors are reacted systematically in individual reaction wells or material sites to form distinct and addressable compounds. Thereafter, active compounds are identified according to their location in or on the array. Another approach, known as encoded mixture synthesis, utilizes various types of chemical tags to identify active compounds. Other combinatorial organic synthetic approaches include the synthesis of a series of compound mixtures, in which specific structural features are attached or modified at each stage. Mixtures are then assayed, with the most active combinations being pursued. Subsequent rounds systematically attach or modify other structural features until manageable numbers of discrete structures can be synthesized and screened.
In general, methods to enhance the throughput of microfluidic applications, including microfluidic screening techniques, would be desirable. The present invention provides new computer implemented methods and associated devices for rapidly contacting or sampling materials in or on arrays having essentially any number of materials sites, with microfluidic devices having essentially any number of capillary elements. The methods have many significant advantages over current approaches, including current combinatorial compound library screens. These and a variety of additional features will become apparent upon complete review of the following.